2024-514730-21-00招募中3 期
A pHase III cluster randomIsed controlled, cross-over, non-inferiority Trial of a short course, High dose AntimicRobials vs conventional dose and Duration in critically ill patients
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 入组人数
- 1,282
- 试验地点
- 14
- 主要终点
- All-cause mortality within 90 days after inclusion.
研究概览
简要总结
To determine the non-inferiority of a short course, high dose antimicrobial therapy in critically ill patients with pneumonia, intra-abdominal infection (IAI) or bloodstream infection (BSI) for all cause 90-day mortality. Our primary hypothesis is that a short course, high dose antimicrobial therapy results in similar outcomes compared to conventional duration and dose, while it results in a lower exposure to antimicrobials.
研究设计
- 分配方式
- Randomized
- 主要目的
- Hit-hard
- 盲法
- None
入排标准
- 年龄范围
- 18 years 至 65+ years（65+ Years, 18-64 Years）
- 接受健康志愿者
- 是
入选标准
- •Age ≥18 years.
- •Patient with (suspicion of) community acquired pneumonia (CAP) or hospital acquired pneumonia (HAP) or ventilator acquired pneumonia (VAP) or intra- abdominal infection (IAI) or bloodstream infection (BSI) for which one of the following antimicrobials has been prescribed or has been commenced: ceftriaxone, cefotaxime, cefuroxime, piperacillin- tazobactam or meropenem. To note: The beta lactam antimicrobial is considered the pivotal antibiotic in a multidrug strategy: co-administration of other – non-study – antibiotics in standard dosage, e.g. to expand the spectrum of the empirical therapy (e.g. vancomycin, aminoglycosides), or because they are recommended in guidelines (e.g. macrolides) is allowed; these antimicrobials will be dosed as per local practice, and data will be collected.
- •Treatment may be empirical or targeted (I.e. based on culture results)
- •Patients must be admitted to the ICU and have to be expected to be hospitalized in the ICU until at least the day after tomorrow.
- •Administering study related antimicrobials using either a short course, high dose treatment or conventional dose and duration treatment, are considered appropriate for the patient. To note: Patients with infections that require a (according to prevailing guidelines) higher than standard dose, or require a longer duration, e.g. endocarditis, Staphylococcus aureus bacteraemia or prosthetic joint infection, osteomyelitis... (non-limitative list) are therefore not to be included. Also patients in who(m) source control is evidently not achieved, cannot be included. Of course, some patients may be included but then need to ‘drop out’ because one of the above-mentioned diagnoses becomes apparent during the course of therapy e.g. S. aureus is cultured from blood in a patient with CAP. This will lead to secondary exclusion of the patient (“drop out”).
- •One or more organ dysfunction criteria in the previous 24 hours and ongoing: - MAP < 60mmHg for at least 1 hours. - Vasopressor required for > 4 hours. - Respiratory support using supplemental high flow nasal oxygen, continuous positive airway pressure, bilevel positive airway pressure or invasive mechanical ventilation for at least 1 hour. - Serum creatinine concentration > 220µmol/L or >2.49 mg/dL.
排除标准
- •Patient is known or suspected to be pregnant.
- •Patient has received the study related antimicrobial for more than 12 hours prior to inclusion in the study.
- •Patient has a proven severe allergy for one of the study antibiotics. To note:In case of a documented non-severe (suspected) allergy for one of the study antibiotics: choice of antibiotic according to local protocol, on discretion of the treating physician.
- •The attending physician or patient or legal representative is not committed to full active treatment. To note: Limitation of cardiopulmonary resuscitation (CPR) only is not an exclusion criterium.
- •The patient is treated for an infection that requires a higher than standard dose or longer than the CONTROL strategy. To note: Patients with infections that require a (according to prevailing guidelines) higher than standard dose, or require a longer duration, e.g. endocarditis, Staphylococcus aureus bacteraemia or prosthetic joint infection, osteomyelitis... (non-limitative list) are therefore not to be included. Also patients in who(m) source control is evidently not achieved, cannot be included. Of course, some patients may be included but then need to ‘drop out’ because one of the above-mentioned diagnoses becomes apparent during the course of therapy e.g. S. aureus is cultured from blood in a patient with CAP. This will lead to secondary exclusion of the patient (“drop out”).
- •The patient has previously been enrolled in the HIT-HARD study.
- •Use of the study related antimicrobial as prophylactic therapy administered as the IV component of SDD strategy, without proven infection. Oral / enteral components of SDD may be used in patients included in the HITHARD study, as long as the pivotal study antibiotic is administered because of an infection as per the inclusion criteria.
- •Patient is requiring renal replacement therapy at the time of randomisation, including renal replacement therapy for chronic kidney disease.
结局指标
主要结局
All-cause mortality within 90 days after inclusion.
All-cause mortality within 90 days after inclusion.
次要结局
- All-cause ICU mortality.
- All-cause hospital mortality.
- New colonization or infection with a multi-resistant organism (MRSA, VRE, MDR P. aeruginosa, CRE, ESBL Enterobacterales, Acinetobacter baumannii) or C. difficile diarrhea/infection up to 28 days post inclusion.
- Antimicrobial free days.
- Recurrence of infection.
- Toxicity.
- Health related quality of life (EQ-5D-5L measured at D90).
- Exposure.
- Clinical cure
- 10. ICU length of stay
- 11. Hospital length of stay
- 12. Organ support free days
- 13. DDDs and DOTs
研究者
Prof. dr. Jan De Waele
Scientific
Universitair Ziekenhuis Gent
研究点 (14)
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